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Synthesis and Structure–Activity Correlation Studies of Secondary‐ and Tertiary‐Amine‐Based Glutathione Peroxidase Mimics
Author(s) -
Bhabak Krishna P.,
Mugesh Govindasamy
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200900818
Subject(s) - chemistry , cumene hydroperoxide , amine gas treating , thiol , glutathione , peroxidase , reactivity (psychology) , catalysis , peroxide , amino acid , organic chemistry , combinatorial chemistry , medicinal chemistry , stereochemistry , enzyme , biochemistry , medicine , alternative medicine , pathology
In this study, a series of secondary‐ and tertiary‐amino‐substituted diaryl diselenides were synthesized and studied for their glutathione peroxidase (GPx) like antioxidant activities with H 2 O 2 , cumene hydroperoxide, or t BuOOH as substrates and with PhSH or glutathione (GSH) as thiol cosubstrates. This study reveals that replacement of the tert ‐amino groups in benzylamine‐based diselenides by sec ‐amino moieties drastically enhances the catalytic activities in both the aromatic thiol (PhSH) and GSH assay systems. Particularly, the N ‐propyl‐ and N ‐isopropylamino‐substituted diselenides are 8–18 times more active than the corresponding N,N ‐dipropyl‐ and N,N ‐diisopropylamine‐based compounds in all three peroxide systems when GSH is used as the thiol cosubstrate. Although the catalytic mechanism of sec ‐amino‐substituted diselenides is similar to that of the tert ‐amine‐based compounds, differences in the stability and reactivity of some of the key intermediates account for the differences in the GPx‐like activities. It is observed that the sec ‐amino groups are better than the tert ‐amino moieties for generating the catalytically active selenols. This is due to the absence of any significant thiol‐exchange reactions in the selenenyl sulfides derived from sec ‐amine‐based diselenides. Furthermore, the seleninic acids (RSeO 2 H) derived from the sec ‐amine‐based compounds are more stable toward further reactions with peroxides than their tert ‐amine‐based analogues.